5610437 HLA TISSUE TYPING AND HSCT FOR THE SICKLE CELL DISEASE COHORT AT THE ROYAL CHILDREN’S HOSPITAL (MELBOURNE, AUSTRALIA): AN AUDIT
Authors: A. Duncan, L. Clucas, E. O’Reilly, A. Greenway
Journal: HemaSphere (2023)

Background: Sickle cell disease (SCD) is a serious and potentially life-threatening condition, of which the only established curative treatment is an allogeneic haematopoietic stem cell transplant (HSCT). HSCT is associated with significant risks, including up to a 10% risk of mortality in SCD1, and hence careful consideration of a patient’s suitability for HSCT is required by clinicians. For paediatric patients with SCD at the Royal Children’s Hospital (RCH), Melbourne, HSCT is considered on a case-by-case basis, with consideration being given to patient and family preferences in conjunction with the available international guidelines. There is currently no available guideline which provides a clear approach regarding the age at which HSCT should first be offered, the timing of which siblings should be investigated as potential donors, or whether HSCT should be offered in the absence of SCD complications. Aim: To determine how many patients from the SCD population treated at our centre have had human leucocyte antigen (HLA) tissue typing, how many proceeded to HSCT and the HSCT outcomes. Method: An audit was performed of the paediatric patients with SCD currently being treated at the RCH. Patient’s electronic medical records and laboratory results were accessed to determine if HLA tissue typing had been performed, if they had a HLA-matched sibling, and whether they had proceeded to HSCT. HSCT engraftment and mortality data was also reviewed. Results: There are currently 54 patients with SCD cared for at our centre. 12 of the 54 (22%) have had HLA typing performed for themselves and their siblings. Of these, eight (67%) do not have an HLA compatible sibling. Four patients (7%) have proceeded to BMT – three had matched sibling donors (MSD), and one patient underwent a haploidentical donor transplant in the absence of a MSD. Two of these patients have successfully engrafted, with >96% donor chimerism at 12 months. Unfortunately, one patient is deceased and the patient who received the haploidentical HSCT had failed engraftment. A fifth BMT is planned (MSD). Summary: Only a small proportion (22%) of SCD patients at our centre have had HLA typing performed for themselves and their siblings. 33% have a HLA-matched sibling, compared with <20% reported internationally2 (limited by small numbers). The small number of patients who have undergone HSCT in our centre demonstrated the variability in possible outcomes. HSCT offers the possibility of cure, but this is not certain, and comes with significant risks. Current ASH guidelines identify three indications for transplant: overt stroke, frequent pain and acute chest syndrome3. In Australia, children with SCD have access to a single disease modifying therapy, hydroxyurea. Voxelotor and Crizanlizumab are not currently approved for use, therefore the trajectory to transplant may be more pre-emptive. Before offering HLA tissue typing to every patient with a sibling, we must consider the potential barriers. Most notably, the significant risk of mortality and morbidity, the financial cost of transplant to the healthcare system compared to lifetime care of a patient with SCD, the availability of bone marrow transplant (BMT) unit beds and the potential implications for patients with malignant disease. Not insignificant, is the psychological cost to patients and their families who pin their hopes on a cure only to be disappointed if they are not an HLA match. References 1, 3. Aydin et al, American Society for Transplantation and Cellular Therapy 2021; 27: 1004.e1 - 1004.e8 2. Kanter et al, Blood Advances 2021; 5: 18